RATIONALE: Neoadjuvant chemotherapy for women with stage II-III Her negative breast cancer followed by Her2Bi armed activated T cells (ATCs) may significantly improve the pathologic complete response (pCR) rate at the time of surgery. Arming ex vivo expanded T cells in the laboratory may help the T cells kill more tumor cells when they are put back in the body. Giving combination neoadjuvant chemotherapy followed by laboratory-treated T cells before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Total of 4 of the T cell infusions intravenously over a period of 1 month.

Drug: cyclophosphamide

As prescribed by physician, standard of care.

Other Name: Cytoxan®

Drug: doxorubicin hydrochloride

As prescribed by physician, standard of care.

Other Names:

Adriamycin®

Rubex®

Drug: paclitaxel

As prescribed by physician, standard of care.

Other Names:

Abraxane®

Onxol®

Taxol

Other: laboratory biomarker analysis

Immune studies will be done pre-immunotherapy, prior to the third infusion of activated T-cells, at the time of surgery, and 1 month after immunotherapy. If there are positive findings, additional optional studies will be done at 3, 6, and 12 months, if the immune studies show changes worthy of follow-up studies.

Procedure: neoadjuvant therapy

As prescribed by physician, standard of care.

Procedure: therapeutic conventional surgery

As recommended by physician, post immunotherapy.

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate progression-free survival (PFS) in women with stage II-III triple-negative breast cancer without a complete pathologic response (cPR) who receive a regimen of neoadjuvant chemotherapy (chemoT), surgery, and/or irradiation followed by 8 infusions of ~10-15 x 10^9 Her2Bi-armed activated T cells (ATC) (aATC) given twice per week for 4 weeks in combination with IL-2 (aldesleukin) (300,000 IU/m^2/day) and GM-CSF (sargramostim) (250 μg/m^2/twice per week) beginning 3 days before the 1st infusion and ending 1 week after the last infusion (defined as immunotherapy).

II. To estimate the change from baseline (pre immunotherapy [IT]) to post-IT in specific cytotoxicity and interferon gamma (IFN-γ) enzyme-linked immunosorbent spots (Elispots) of lymphocytes in the blood directed at breast cancer cells.

III. To investigate if pathologic response and the changes in numbers and proportion of infiltrating cells and cancer stem cells in the tumor at the time of surgery are associated with progressive disease.

Patients may have lymph node positive or negative disease, as long as they have clinical/pathologic stage II or IIIB breast cancer; patients may have the lymph nodes assessed by any method deemed appropriate by the treating physicians, including pre-neoadjuvant therapy sentinel lymph node biopsy

Presence of residual disease measuring at least 5mm (as single foci or in aggregate) on final pathology following surgery

Total bilirubin must be =< the upper limit of normal (ULN) for the lab unless the patient has a grade 1 bilirubin elevation (> ULN to 1.5 x ULN) resulting from Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and

Alkaline phosphatase and AST/ALT may not both be > the ULN; for example, if the alkaline phosphatase is > the ULN but =< 2.5 x ULN, then the AST/ALT must be =< the ULN; if the AST/ALT is > the ULN but =< 1.5 x ULN, then the alkaline phosphatase must be =< ULN

Patients with either skeletal pain or alkaline phosphatase that is > ULN must have a bone scan showing they do not have metastatic disease; suspicious findings on bone scan must be confirmed as benign by x-ray, magnetic resonance imaging (MRI), or biopsy

Patients with AST/ALT or alkaline phosphatase > ULN must have liver imaging that does not demonstrate metastatic disease

Patients with AST/ALT > ULN must have negative hepatitis studies

Patients with stage II disease and clinical suspicion for metastatic disease based on reported symptoms, physical examination findings, or laboratory abnormalities must have staging studies demonstrating no evidence of metastatic disease (with exception of axillary lymph nodes or mammary nodes); patients with stage IIIA disease must have staging studies demonstrating no evidence of metastatic disease (with exception of axillary lymph nodes or mammary nodes), even if asymptomatic with normal physical examination and laboratory values; such staging studies must include: chest imaging (chest X-ray, computed tomography [CT], or MRI), abdominal/pelvis imaging (CT or MRI), and bone imaging (bone scan or positron emission tomography [PET]-scan); abnormalities that are indeterminate and too small to biopsy should be followed with further imaging, as appropriate, but do not exclude patients from the study; abnormalities that are suspicious and large enough to biopsy exclude patients from the study, unless a biopsy is performed and is negative for metastatic disease

Prior history of invasive breast cancer (patients with a history of DCIS or lobular carcinoma in situ [LCIS] are eligible)

Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization and is deemed by the physician to be at low risk for recurrence; patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell or squamous cell carcinoma of the skin

Known cardiac disease which precludes their ability to receive planned treatments:

Angina pectoris that requires the use of anti-anginal medication

History of documented congestive heart failure

Serious cardiac arrhythmia requiring medication

Severe conduction abnormality

Valvular disease with documented cardiac function compromise; and

Uncontrolled hypertension defined as blood pressure (BP) that is consistently > 150/90 on antihypertensive therapy at the time of registration (Patients with hypertension that is well controlled on medication are eligible)

History of myocardial infarction (MI) documented by elevated cardiac enzymes with persistent regional wall motion abnormality on assessment of left ventricular (LV) function (patients with history of MI must have an echo instead of/in addition to a MUGA to evaluate LV wall motion)

Symptomatic peripheral vascular disease

Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude treatment with any of the treatment regimens or would prevent required follow-up

Chronic ongoing oral steroid use at the time of registration for any condition (such as asthma, rheumatoid arthritis, etc)

Administration of any investigational agents within 30 days before study entry

Pregnancy or lactation at the time of registration

Psychiatric or addictive disorders or other conditions that in the opinion of the investigators would preclude the patient from complying with the study protocol

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01147016